Prolonged in vivo residence times of llama single-domain antibody fragments in pigs by binding to porcine immunoglobulins

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• 作者：Michiel M. Harmsen ; Conny B. Van Solt ; Helmi P.D. Fijten and Marga C. Van Setten
• 关键词：Single-domain antibody ; Vaccination ; Clearance
• 刊名：Vaccine
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：23
• 期：41
• 页码：4926-4934
• 全文大小：177 K

文摘

The therapeutic parenteral application of llama single-domain antibody fragments (VHHs) is hampered by their small size, resulting in a fast elimination from the body. Here we describe a method to increase the serum half-life of VHHs in pigs by fusion to another VHH binding to porcine immunoglobulin G (pIgG). We isolated 19 pIgG-binding VHHs from an immunized llama using phage display. Six VHHs were genetically fused to model VHH K609 that binds to Escherichia coli F4 fimbriae. All six yeast-produced genetic fusions of two VHH domains (VHH2s) were functional in ELISA and bound to pIgG with high affinity (1–33 nM). Four pIgG-binding VHH2s were administered to pigs and showed a 100-fold extended in vivo residence times as compared to a control VHH2 that does not bind to pIgG. This could provide the basis for therapeutic application of VHHs in pigs.